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Postremission therapy in older adults with acute myeloid leukemia: an opportunity for new drug development

Leukemia volume 16, pages 745–747 (2002)Cite this article

The difficulties encountered in treating older patients with acute myeloid leukemia (AML) are well known and include problems due to leukemia cell drug resistance and decreased tolerance of the side-effects of therapy. The definition of ‘old’ in treatment protocols has changed over the years, in part related to the increasing age at which allogeneic transplantation can be safely applied. Although the current arbitrary breakpoint at age 60 years seems to effectively distinguish patients with markedly different prognoses, there is likely to be a continuum of worsening outcome in patients in the 40–60-year-old group as well. Even in patients with apparent ‘de novo’ AML, CALGB trials consistently show long-term survival in only about 7% of older patients with AML.1 Results in patients not selected for clinical trials may be even worse since certain minimal levels of organ function are required for entry on such protocols. In addition, as evidenced by the high incidence of unfavorable karyotypic changes found in older AML patients, a considerable fraction of patients probably had antecedent marrow disorders, which were not obvious from the patient's history.

Leukemias in older patients probably derive from a cell that is close to the hematopoietic stem cell. Hematopoietic precursors are designed to survive the repeated exposures to environmental (including bacterial and fungal) toxins, which are expected to be encountered during a lifetime. Virtually all resistance mechanisms that have been studied to date have been overexpressed in such cells. As demonstrated by marrow purging experiments, the hematopoietic stem cell can survive exposure to very large doses of cytotoxic agents in vitro. It is not surprising, therefore, that leukemias deriving from such immature progenitors are particularly resistant to cytotoxic agents. Indeed the complexity of the mutations in AML in older patients or in those with prior myelodysplasia may be more analogous to the multiple changes found in epithelial cancers than to the balanced translocations common in AML in younger patients. Thus, it would be surprising if cytotoxic agents turn out to be the long-term answer in the treatment of this disease.

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  1. Karmanos Cancer Institute and the Division of Hematology/Oncology, Wayne State University School of Medicine, Detroit, MI, USA

    CA Schiffer

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This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum, San Francisco, 20 April 2001. Supported by an unrestricted educational grant from Immunex.

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Schiffer, C. Postremission therapy in older adults with acute myeloid leukemia: an opportunity for new drug development. Leukemia 16, 745–747 (2002). https://doi.org/10.1038/sj.leu.2402487

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